Our overall goal is to develop new strategies to enhance the recovery of upper-limb function after spinal cord injury (SCI). We propose to use modern electrophysiological methods to enhance the efficacy of residual corticospinal connections. Defining the neural basis by which corticospinal volleys generate muscle responses will provide crucial information required to maximize residual motor output. Our specific goals are to: 1) determine the temporal organization of corticospinal volleys and location of motor cortical representations of upper-limb muscles after incomplete cervical SCI and 2) develop methodologies to promote recovery of function. We focus on reach and grasp movements because of their importance in daily life activities. Multiple descending volleys in the corticospinal tract generate multiple peaks in muscle responses (indirect (I) - waves). In Aim 1, paired transcranial magnetic stimulation (TMS) will be used to examine I-waves in surface electromyographic (EMG) recordings of upper-limb muscles during reach and grasp. The temporal organization of the early and late I-waves and contribution to voluntary EMG activity will be determined. In Aim 2, the size (and location) of cortical maps of upper-limb muscles will be defined using TMS guided by a frameless magnetic resonance imaging neuronavigation system. Together, these studies in individuals with and without SCI will determine mechanisms of corticospinal reorganization during reach and grasp. In Aim 3, we will use novel TMS paradigms to maximize the effectiveness of residual corticospinal connections by engaging mechanisms of corticospinal reorganization. Repeated paired-TMS will target functionally relevant I- wave intervals at affected motor cortical locations. Training of reach and grasp movements will be combined with paired-TMS-paradigms to further enhance behaviorally relevant plasticity and recovery of function. The proposed experiments will provide new knowledge on mechanisms of corticospinal reorganization involving reach and grasp movements which will be used to guide functionally-relevant plasticity-inducing protocols to enhance recovery. There are no universally accepted treatments for upper-limb motor disability after SCI and other CNS disorders that affect the corticospinal pathway. Current treatments for reach and grasp functions result in limited improvements. Thus, there is a pressing need to develop new strategies to promote recovery of meaningful function after SCI.